PB2051: PRIMARY MYELOFIBROSIS IN YOUNG PATIENTS ≤50 YEARS: CLINICOPATHOLOGICAL CHARACTERISTICS, GENETIC LANDSCAPE AND DISEASE OUTCOME. A SINGLE CENTER EXPERIENCE
Authors: S. Elkourashy, D. Soliman, P. Chandra, R. Taha, H. Elomri
Journal: HemaSphere (2022)

Background: Primary Myelofibrosis (PMF) is a rare myeloproliferative neoplasm, often diagnosed in the 6th and 7th decade. Approximately 5 and 17% of the patients are diagnosed before the age of 40 and 50 years, respectively. Aims: Here, we aim to analyze PMF patients by age group, comparing young patients (≤50 years) to older age group, in terms of clinical, pathologic, genetic profile, treatment history and outcomes. Methods: This is a single center retrospective study carried out in National Center for Cancer Care and Research, Hamad Medical Corporation over the period 2008-2021. We identified WHO-defined PMF patients and collected their demographic data, bone marrow findings, driver mutations, clinical and hematologic characteristics. DIPSS-Plus score was calculated as well. Time to progression, was considered as the time to acquisition of ≥1 of the following: Hemoglobin < 10 g/dl, Leukocyte count >25 x109/L, Platelet count < 100 x109/L, Circulating blast cells ≥1%, transfusion dependency. Overall survival (OS) and progression free survival (PFS) were assessed using Kaplan-Meier method. Results: A total of 61 patients identified, from which 33(54.1%) were ≤50 years at the time of diagnosis. The median age at diagnosis was 39 years (range 24-50). 51.5% had prefibrotic MF. Females accounted for 51.5%. DIPPS-Plus at diagnosis was calculated, 12 patients (36.4%) were low, 11(33.3%) intermediate-1, 8(24.2%) intermediate-2, and 2(6.1%) high-risk. Driver mutations; JAK2 mutation was detected in 19/33(57.6%), CALR in 10/26 (38.5%), MPL in 1/6 (16.7%) and only 1 was triple-negative. 30 patients had cytogenetic information. 29/30(96.7%) showed favorable Karyotype (of which 27 had normal Karyotype). Around half of patients showed disease progression and two third (23 patients) need treatment eventually mainly Cytoreduction 18/23 (78.3%) then Ruxolitinib 11/23 (47.8%), 1 underwent Bone marrow transplant (BMT). Complications include thrombosis in 21.2% and refractory anemia 33.3% with transfusion need in 21.2%, but no leukemic transformation. 28 patients (84.8%) were alive over follow up period. Comparison between 2 studied groups were summarized in Table 1. Three patients died in the age group >50 years and one patient died in age group ≤50 years. No statistically significant difference observed in median OS between age ≤50 years (median 276.9 months, 75th percentile 276.8 months) and > 50 years (median 315.9 months, 75th percentile 108.7 months) (Log rank test P-value 0.494). The median PFS was observed to be higher in patients with age ≤50 years (median PFS 249.8 months, 75th percentile 249.8 months) compared to patients with age >50 years (median PFS 105.3 months, 75th percentile 93.04 months), however this observed difference was statistically insignificant (Log rank test P-value 0.172). Image:Summary/Conclusion: PMF is rarely diagnosed in patients ≤ 50 years old (estimated < 20%), but surprisingly it constitutes > 50% of our cohort. Young patients showed female predominance, more favorable cytogenetics, lower risk-score categories, better disease outcome and no AML transformation. Interestingly, the young group displayed higher median Lactate dehydrogenase level which is marker of cell turnover, and corelated as well with higher median leucocyte and peripheral blast count, along with more frequent splenomegaly and constitutional symptoms indicating prominent clonal myeloproliferation. No difference between the two groups regarding the degree of anemia, platelets counts and disease complications. The prognosis in these patients seems more favorable with higher median PFS over the observed period of follow up.